PreCheck for intestinal immunity

Immune cells act as TSA screeners in the intestine—tolerating commensal microbes and food antigens but remaining vigilant against attack. However, it has remained unclear how T cell precursors differentiate into the different cell types required to perform this balancing act. Now, Bilate et al. report that the T cell receptor (TCR) itself does not limit T cell fate to a single identity. The authors found that cells expressing a single TCR derived from a peripheral regulatory T cell (Treg) developed into either Tregs or CD4+CD8αα+ intraepithelial lymphocytes (CD4IELs) in the gut. This differentiation depended on cues from both the microbiota and the surrounding environment.